Daniel Castro‐Pereira, MD

Over the past decade, the use of chest computed tomography scans with pulmonary angiography (CTPA) for diagnosis of pulmonary embolism (PE) has soared due to the ease of acquisition, the desire for the additional information that CT scanning may provide, and heightened sensitivity to medical liability.[1, 2, 3, 4, 5, 6] In parallel with this shift, the incidence of PE has nearly doubled, despite no recorded increase in the pretest probability of the disease, increasing from 62 per 100,000 to 112 per 100,000 during the period of 1993 to 2006.⁶ One major explanation for this increase is that the improvement in CTPA resolution has enabled radiologists to identify more small peripheral (ie, segmental and subsegmental) filling defects. When confronted with the finding of a small peripheral filling defect on CTPA, clinicians often face a management quandary. Case series and retrospective series on outcomes of these patients do not support treatment, but they are limited by having small numbers of patients; the largest examined 93 patients and provided no insight into the treatment decision.[7] Uncertainty exists, furthermore, about the pathologic meaning of small peripheral filling defects.[8] Clinicians must weigh these arguments and the risk of anticoagulation against concerns about the consequences of untreated pulmonary thromboemboli. More information is needed, therefore, on the outcomes of patients with peripheral filling defects, and on variables impacting the treatment decision, in order to help clinicians manage these patients.[9]

In this study, we analyzed cases of patients with a single peripheral filling defect (SPFD). We choose to look at patients with a SPFD because they represent the starkest decision‐making treatment dilemma and are not infrequent. We assessed the 90‐day mortality and rate of postdischarge venous thromboembolism (VTE) of treated and untreated patients and identified characteristics of treated and untreated patients with a SPFD. We wished to determine the incidence of SPFD among patients evaluated with CTPA and to determine how often the defect is called a PE by the radiologist. We also aimed to determine what role secondary studies play in helping to clarify the diagnosis and management of SPFD and to identify other factors that may influence the decision to treat patients with this finding.

METHODS

RESULTS

A total of 4906 CTPAs were screened during the 66 months reviewed, identifying 518 (10.6%) with any filling defect and 153 (3.1%) with a SPFD. Thirteen patients were excluded from the primary analysis because their records could not be located, and another 6 were excluded because they had a concurrently positive CUS. The primary analysis was performed, therefore, with 134 patients. The inpatient service ordered 78% of the CTPAs. The initial radiologist stated in the impression section of the report that a PE was present in 99 of 134 (73.9%) studies. On over‐read of the 134 studies, 100 of these were considered to be positive for a PE. There was modest agreement between the initial impression and the consensus impression at over‐read (=0.69).

DISCUSSION

This very large retrospective study examines treatment and outcomes in patients with a SPFD. We found that SPFDs were common, showing up in approximately 3% of all the CTPAs performed. Among the studies that were deemed positive for PE, SPFD comprised nearly one‐third. Treatment of SPFD, whether concluded as PE or not, was not associated with a mortality benefit or difference in postdischarge VTE within 90 days. Our results add to the weight of smaller case‐control and retrospective series that also found no benefit from treating small PE.[7, 12, 13, 14, 15]

Given this data, why might physicians choose to treat? Physicians may feel compelled to anticoagulate due to extrapolation of data from the early studies showing a fatality rate of up to 30% in untreated PE.[2] Also, physicians may harbor the concern that, though small emboli may pose no immediate danger, they serve as a marker of hypercoagulability and as such are a harbinger of subsequent large clots. A reflexive treatment response to the radiologist's conclusion that the filling defect is a PE may also play a part. Balancing this concern is the recognition that the treatment for acute PE is not benign. The age‐adjusted incidence of major bleeding (eg, gastrointestinal or intracranial) with warfarin has increased by 71%, from 3.1 to 5.3 per 100,000, since the introduction of CTPA.[6] Also, as seen in this study, a substantial percentage of patients will incur the morbidity and cost of IVC‐filter placement.

When physicians face management uncertainty, they consider risk factors for the condition investigated, consult experts, employ additional studies, and weigh patient preference. In this study, history of immobility and VTE were, indeed, positively associated with treatment, but change in mental status was negatively so. Given that the PESI score is higher with change in mental status, this finding is superficially paradoxical but unsurprising. Mental‐status change could not likely stem from a SPFD and its presence heightens the risks of anticoagulation, hence dissuading treatment. Pulmonary consultations were documented in less than half of the cases and did not clearly sway the treatment decision. Determining whether more patients would have been treated if pulmonologists were not involved would require a prospective study.

The most important association with treatment was how the radiologist interpreted the SPFD. Even then, the influence of the radiologist's interpretation was far from complete: 40% of the cases in which PE was called went untreated, and 4 cases received treatment despite PE not being called. The value of the radiologist's interpretation is further undercut by the modest interobserver agreement found on over‐read, which is line with previous reports and reflective of lack of a gold standard for diagnosing isolated peripheral PE.[3, 12, 16]

Even if radiologists could agree upon what they are seeing, the question remains about the pathological importance. Unrecognized PE incidental to the cause of death are commonly found at autopsy. Autopsy studies reveal that up to 52% to 64% of patients have PE; and, if multiple blocks of lung tissue are studied, the prevalence increases up to 90%.[17, 18] In the series by Freiman et al., 59% of the identified thrombi were small enough not to be recognized on routine gross examination.[17] Furthermore, an unknown percentage of small clots, especially in the upper lobes, are in situ thrombi rather than emboli.[18] In the case of small dot‐like clots, Suh and colleagues have speculated that they represent normal embolic activity from the lower limbs, which are cleared routinely by the lung serving in its role as a filter.[19] Although our study only examined SPFD, the accumulation of small emboli could have pathologic consequences. In their review, Gali and Kim reported that 12% of patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary endarterectomy had disease confined to the distal segmental and subsegmental arteries.[13]

Use of secondary studies could mitigate some of the diagnostic and management uncertainty, but they were obtained in only about a quarter of the cases. The use of a second lung‐imaging study following CTPA is not recommended in guidelines or diagnostic algorithms, but in our institution a significant minority of physicians were employing these tests to clarify the nature of the filling defects.[20] Tapson, speaking to the treatment dilemma that small PEs present, has suggested that prospective trials on this topic employ tests that investigate risk for poor outcome if untreated including cardiopulmonary reserve, D‐dimer, and presence of lower‐limb thrombus.[21] Indeed, a study is ongoing examining the outcome at 90 days of patients with single or multiple subsegmental embolism with negative CUS.[22]

Ten of the 134 patients (7.4%) with peripheral filling defects died within 90 days. It is difficult to establish whether these deaths were PE‐specific mortalities because there was a high degree of comorbid illness in this cohort. Five of the 134 (3.7%) had recurrent VTE, which is comparable to the outcomes in other studies.[23]

There are limitations to this study. This study is the first to limit analysis of the filling defects to single defects in the segmental or subsegmental pulmonary arteries. This subset of patients includes those with the least clot burden, therefore representing the starkest decision‐making treatment dilemma, and the incidence of these clots is not insignificant. As a retrospective study, we could not fully capture all of the considerations that may have factored into the clinicians' decision‐making regarding treatment, including patient preference. Because of inadequate documentation, especially in the emergency department notes, we were unable to calculate pretest probability. Also, we cannot exclude that subclinical VTEs were occurring that would later harm the patients. We did not analyze the role of D‐dimer testing because that test is validated to guide the decision to obtain lung‐imaging studies and not to inform the treatment decision. In our cohort, 89 of 134 (66%) of our patients were already hospitalized for other diagnoses prior to PE being queried. Moreover, many of these patients had active malignancy or were being treated for pneumonia, which would decrease the positive predictive value of the D‐dimer test. D‐dimer performs poorly when used for prognosis.[24] This is a single‐center study, therefore the comparability of our findings to other centers may be an issue, although our findings generally accord with those from other single‐center studies.[7, 12, 24, 25] We determined the recurrence rate from the hospital records and could have missed cases diagnosed elsewhere. However, our hospital is the only one in the city and serves the vast majority of patients in the area, and 88% of our cohort had a repeat visit to our hospital subsequently. In addition, the radiology service is the only one in the area that provides outpatient CUS, CTPA, and ventilation‐perfusion scan studies. Our study is the largest to date on this issue. However, our sample size is somewhat modest, and consequently the factors associated with treatment have large confidence intervals. We are therefore constrained in recommending empiric application of our findings. Nonetheless, our results in terms of no difference in mortality and recurrence between treated and untreated patients are in keeping with other studies on this topic. Also, our simulation analysis did reveal factors that were highly associated with the decision to treat. These findings as a whole strongly point to the need for a larger study on this issue, because, as we and other authors have argued, the consequences of treatment are not benign.[6]

In conclusion, this study shows that SPFDs are common and that there was no difference in 90‐day mortality between treated and untreated patients, regardless of whether the defects were interpreted as PE or not. Physicians appear to rely heavily on the radiologist's interpretation for their treatment decision, but they will also treat when the interpretation is not PE and not infrequently abstain when it is. Treatment remains common despite the modest agreement among radiologists whether the peripheral filling defect even represents PE. When secondary imaging studies are obtained and negative, physicians forgo treatment. Larger studies are needed to help clarify our findings and should include decision‐making algorithms that include secondary imaging studies, because these studies may provide enough reassurance when negative to sway physicians against treatment.

Over the past decade, the use of chest computed tomography scans with pulmonary angiography (CTPA) for diagnosis of pulmonary embolism (PE) has soared due to the ease of acquisition, the desire for the additional information that CT scanning may provide, and heightened sensitivity to medical liability.[1, 2, 3, 4, 5, 6] In parallel with this shift, the incidence of PE has nearly doubled, despite no recorded increase in the pretest probability of the disease, increasing from 62 per 100,000 to 112 per 100,000 during the period of 1993 to 2006.⁶ One major explanation for this increase is that the improvement in CTPA resolution has enabled radiologists to identify more small peripheral (ie, segmental and subsegmental) filling defects. When confronted with the finding of a small peripheral filling defect on CTPA, clinicians often face a management quandary. Case series and retrospective series on outcomes of these patients do not support treatment, but they are limited by having small numbers of patients; the largest examined 93 patients and provided no insight into the treatment decision.[7] Uncertainty exists, furthermore, about the pathologic meaning of small peripheral filling defects.[8] Clinicians must weigh these arguments and the risk of anticoagulation against concerns about the consequences of untreated pulmonary thromboemboli. More information is needed, therefore, on the outcomes of patients with peripheral filling defects, and on variables impacting the treatment decision, in order to help clinicians manage these patients.[9]

In this study, we analyzed cases of patients with a single peripheral filling defect (SPFD). We choose to look at patients with a SPFD because they represent the starkest decision‐making treatment dilemma and are not infrequent. We assessed the 90‐day mortality and rate of postdischarge venous thromboembolism (VTE) of treated and untreated patients and identified characteristics of treated and untreated patients with a SPFD. We wished to determine the incidence of SPFD among patients evaluated with CTPA and to determine how often the defect is called a PE by the radiologist. We also aimed to determine what role secondary studies play in helping to clarify the diagnosis and management of SPFD and to identify other factors that may influence the decision to treat patients with this finding.

METHODS

RESULTS

A total of 4906 CTPAs were screened during the 66 months reviewed, identifying 518 (10.6%) with any filling defect and 153 (3.1%) with a SPFD. Thirteen patients were excluded from the primary analysis because their records could not be located, and another 6 were excluded because they had a concurrently positive CUS. The primary analysis was performed, therefore, with 134 patients. The inpatient service ordered 78% of the CTPAs. The initial radiologist stated in the impression section of the report that a PE was present in 99 of 134 (73.9%) studies. On over‐read of the 134 studies, 100 of these were considered to be positive for a PE. There was modest agreement between the initial impression and the consensus impression at over‐read (=0.69).

DISCUSSION

This very large retrospective study examines treatment and outcomes in patients with a SPFD. We found that SPFDs were common, showing up in approximately 3% of all the CTPAs performed. Among the studies that were deemed positive for PE, SPFD comprised nearly one‐third. Treatment of SPFD, whether concluded as PE or not, was not associated with a mortality benefit or difference in postdischarge VTE within 90 days. Our results add to the weight of smaller case‐control and retrospective series that also found no benefit from treating small PE.[7, 12, 13, 14, 15]

Given this data, why might physicians choose to treat? Physicians may feel compelled to anticoagulate due to extrapolation of data from the early studies showing a fatality rate of up to 30% in untreated PE.[2] Also, physicians may harbor the concern that, though small emboli may pose no immediate danger, they serve as a marker of hypercoagulability and as such are a harbinger of subsequent large clots. A reflexive treatment response to the radiologist's conclusion that the filling defect is a PE may also play a part. Balancing this concern is the recognition that the treatment for acute PE is not benign. The age‐adjusted incidence of major bleeding (eg, gastrointestinal or intracranial) with warfarin has increased by 71%, from 3.1 to 5.3 per 100,000, since the introduction of CTPA.[6] Also, as seen in this study, a substantial percentage of patients will incur the morbidity and cost of IVC‐filter placement.

When physicians face management uncertainty, they consider risk factors for the condition investigated, consult experts, employ additional studies, and weigh patient preference. In this study, history of immobility and VTE were, indeed, positively associated with treatment, but change in mental status was negatively so. Given that the PESI score is higher with change in mental status, this finding is superficially paradoxical but unsurprising. Mental‐status change could not likely stem from a SPFD and its presence heightens the risks of anticoagulation, hence dissuading treatment. Pulmonary consultations were documented in less than half of the cases and did not clearly sway the treatment decision. Determining whether more patients would have been treated if pulmonologists were not involved would require a prospective study.

The most important association with treatment was how the radiologist interpreted the SPFD. Even then, the influence of the radiologist's interpretation was far from complete: 40% of the cases in which PE was called went untreated, and 4 cases received treatment despite PE not being called. The value of the radiologist's interpretation is further undercut by the modest interobserver agreement found on over‐read, which is line with previous reports and reflective of lack of a gold standard for diagnosing isolated peripheral PE.[3, 12, 16]

Even if radiologists could agree upon what they are seeing, the question remains about the pathological importance. Unrecognized PE incidental to the cause of death are commonly found at autopsy. Autopsy studies reveal that up to 52% to 64% of patients have PE; and, if multiple blocks of lung tissue are studied, the prevalence increases up to 90%.[17, 18] In the series by Freiman et al., 59% of the identified thrombi were small enough not to be recognized on routine gross examination.[17] Furthermore, an unknown percentage of small clots, especially in the upper lobes, are in situ thrombi rather than emboli.[18] In the case of small dot‐like clots, Suh and colleagues have speculated that they represent normal embolic activity from the lower limbs, which are cleared routinely by the lung serving in its role as a filter.[19] Although our study only examined SPFD, the accumulation of small emboli could have pathologic consequences. In their review, Gali and Kim reported that 12% of patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary endarterectomy had disease confined to the distal segmental and subsegmental arteries.[13]

Use of secondary studies could mitigate some of the diagnostic and management uncertainty, but they were obtained in only about a quarter of the cases. The use of a second lung‐imaging study following CTPA is not recommended in guidelines or diagnostic algorithms, but in our institution a significant minority of physicians were employing these tests to clarify the nature of the filling defects.[20] Tapson, speaking to the treatment dilemma that small PEs present, has suggested that prospective trials on this topic employ tests that investigate risk for poor outcome if untreated including cardiopulmonary reserve, D‐dimer, and presence of lower‐limb thrombus.[21] Indeed, a study is ongoing examining the outcome at 90 days of patients with single or multiple subsegmental embolism with negative CUS.[22]

Ten of the 134 patients (7.4%) with peripheral filling defects died within 90 days. It is difficult to establish whether these deaths were PE‐specific mortalities because there was a high degree of comorbid illness in this cohort. Five of the 134 (3.7%) had recurrent VTE, which is comparable to the outcomes in other studies.[23]

There are limitations to this study. This study is the first to limit analysis of the filling defects to single defects in the segmental or subsegmental pulmonary arteries. This subset of patients includes those with the least clot burden, therefore representing the starkest decision‐making treatment dilemma, and the incidence of these clots is not insignificant. As a retrospective study, we could not fully capture all of the considerations that may have factored into the clinicians' decision‐making regarding treatment, including patient preference. Because of inadequate documentation, especially in the emergency department notes, we were unable to calculate pretest probability. Also, we cannot exclude that subclinical VTEs were occurring that would later harm the patients. We did not analyze the role of D‐dimer testing because that test is validated to guide the decision to obtain lung‐imaging studies and not to inform the treatment decision. In our cohort, 89 of 134 (66%) of our patients were already hospitalized for other diagnoses prior to PE being queried. Moreover, many of these patients had active malignancy or were being treated for pneumonia, which would decrease the positive predictive value of the D‐dimer test. D‐dimer performs poorly when used for prognosis.[24] This is a single‐center study, therefore the comparability of our findings to other centers may be an issue, although our findings generally accord with those from other single‐center studies.[7, 12, 24, 25] We determined the recurrence rate from the hospital records and could have missed cases diagnosed elsewhere. However, our hospital is the only one in the city and serves the vast majority of patients in the area, and 88% of our cohort had a repeat visit to our hospital subsequently. In addition, the radiology service is the only one in the area that provides outpatient CUS, CTPA, and ventilation‐perfusion scan studies. Our study is the largest to date on this issue. However, our sample size is somewhat modest, and consequently the factors associated with treatment have large confidence intervals. We are therefore constrained in recommending empiric application of our findings. Nonetheless, our results in terms of no difference in mortality and recurrence between treated and untreated patients are in keeping with other studies on this topic. Also, our simulation analysis did reveal factors that were highly associated with the decision to treat. These findings as a whole strongly point to the need for a larger study on this issue, because, as we and other authors have argued, the consequences of treatment are not benign.[6]

In conclusion, this study shows that SPFDs are common and that there was no difference in 90‐day mortality between treated and untreated patients, regardless of whether the defects were interpreted as PE or not. Physicians appear to rely heavily on the radiologist's interpretation for their treatment decision, but they will also treat when the interpretation is not PE and not infrequently abstain when it is. Treatment remains common despite the modest agreement among radiologists whether the peripheral filling defect even represents PE. When secondary imaging studies are obtained and negative, physicians forgo treatment. Larger studies are needed to help clarify our findings and should include decision‐making algorithms that include secondary imaging studies, because these studies may provide enough reassurance when negative to sway physicians against treatment.

Over the past decade, the use of chest computed tomography scans with pulmonary angiography (CTPA) for diagnosis of pulmonary embolism (PE) has soared due to the ease of acquisition, the desire for the additional information that CT scanning may provide, and heightened sensitivity to medical liability.[1, 2, 3, 4, 5, 6] In parallel with this shift, the incidence of PE has nearly doubled, despite no recorded increase in the pretest probability of the disease, increasing from 62 per 100,000 to 112 per 100,000 during the period of 1993 to 2006.⁶ One major explanation for this increase is that the improvement in CTPA resolution has enabled radiologists to identify more small peripheral (ie, segmental and subsegmental) filling defects. When confronted with the finding of a small peripheral filling defect on CTPA, clinicians often face a management quandary. Case series and retrospective series on outcomes of these patients do not support treatment, but they are limited by having small numbers of patients; the largest examined 93 patients and provided no insight into the treatment decision.[7] Uncertainty exists, furthermore, about the pathologic meaning of small peripheral filling defects.[8] Clinicians must weigh these arguments and the risk of anticoagulation against concerns about the consequences of untreated pulmonary thromboemboli. More information is needed, therefore, on the outcomes of patients with peripheral filling defects, and on variables impacting the treatment decision, in order to help clinicians manage these patients.[9]

In this study, we analyzed cases of patients with a single peripheral filling defect (SPFD). We choose to look at patients with a SPFD because they represent the starkest decision‐making treatment dilemma and are not infrequent. We assessed the 90‐day mortality and rate of postdischarge venous thromboembolism (VTE) of treated and untreated patients and identified characteristics of treated and untreated patients with a SPFD. We wished to determine the incidence of SPFD among patients evaluated with CTPA and to determine how often the defect is called a PE by the radiologist. We also aimed to determine what role secondary studies play in helping to clarify the diagnosis and management of SPFD and to identify other factors that may influence the decision to treat patients with this finding.

METHODS

RESULTS

A total of 4906 CTPAs were screened during the 66 months reviewed, identifying 518 (10.6%) with any filling defect and 153 (3.1%) with a SPFD. Thirteen patients were excluded from the primary analysis because their records could not be located, and another 6 were excluded because they had a concurrently positive CUS. The primary analysis was performed, therefore, with 134 patients. The inpatient service ordered 78% of the CTPAs. The initial radiologist stated in the impression section of the report that a PE was present in 99 of 134 (73.9%) studies. On over‐read of the 134 studies, 100 of these were considered to be positive for a PE. There was modest agreement between the initial impression and the consensus impression at over‐read (=0.69).

DISCUSSION

This very large retrospective study examines treatment and outcomes in patients with a SPFD. We found that SPFDs were common, showing up in approximately 3% of all the CTPAs performed. Among the studies that were deemed positive for PE, SPFD comprised nearly one‐third. Treatment of SPFD, whether concluded as PE or not, was not associated with a mortality benefit or difference in postdischarge VTE within 90 days. Our results add to the weight of smaller case‐control and retrospective series that also found no benefit from treating small PE.[7, 12, 13, 14, 15]

Given this data, why might physicians choose to treat? Physicians may feel compelled to anticoagulate due to extrapolation of data from the early studies showing a fatality rate of up to 30% in untreated PE.[2] Also, physicians may harbor the concern that, though small emboli may pose no immediate danger, they serve as a marker of hypercoagulability and as such are a harbinger of subsequent large clots. A reflexive treatment response to the radiologist's conclusion that the filling defect is a PE may also play a part. Balancing this concern is the recognition that the treatment for acute PE is not benign. The age‐adjusted incidence of major bleeding (eg, gastrointestinal or intracranial) with warfarin has increased by 71%, from 3.1 to 5.3 per 100,000, since the introduction of CTPA.[6] Also, as seen in this study, a substantial percentage of patients will incur the morbidity and cost of IVC‐filter placement.

When physicians face management uncertainty, they consider risk factors for the condition investigated, consult experts, employ additional studies, and weigh patient preference. In this study, history of immobility and VTE were, indeed, positively associated with treatment, but change in mental status was negatively so. Given that the PESI score is higher with change in mental status, this finding is superficially paradoxical but unsurprising. Mental‐status change could not likely stem from a SPFD and its presence heightens the risks of anticoagulation, hence dissuading treatment. Pulmonary consultations were documented in less than half of the cases and did not clearly sway the treatment decision. Determining whether more patients would have been treated if pulmonologists were not involved would require a prospective study.

The most important association with treatment was how the radiologist interpreted the SPFD. Even then, the influence of the radiologist's interpretation was far from complete: 40% of the cases in which PE was called went untreated, and 4 cases received treatment despite PE not being called. The value of the radiologist's interpretation is further undercut by the modest interobserver agreement found on over‐read, which is line with previous reports and reflective of lack of a gold standard for diagnosing isolated peripheral PE.[3, 12, 16]

Even if radiologists could agree upon what they are seeing, the question remains about the pathological importance. Unrecognized PE incidental to the cause of death are commonly found at autopsy. Autopsy studies reveal that up to 52% to 64% of patients have PE; and, if multiple blocks of lung tissue are studied, the prevalence increases up to 90%.[17, 18] In the series by Freiman et al., 59% of the identified thrombi were small enough not to be recognized on routine gross examination.[17] Furthermore, an unknown percentage of small clots, especially in the upper lobes, are in situ thrombi rather than emboli.[18] In the case of small dot‐like clots, Suh and colleagues have speculated that they represent normal embolic activity from the lower limbs, which are cleared routinely by the lung serving in its role as a filter.[19] Although our study only examined SPFD, the accumulation of small emboli could have pathologic consequences. In their review, Gali and Kim reported that 12% of patients with chronic thromboembolic pulmonary hypertension who underwent pulmonary endarterectomy had disease confined to the distal segmental and subsegmental arteries.[13]

Use of secondary studies could mitigate some of the diagnostic and management uncertainty, but they were obtained in only about a quarter of the cases. The use of a second lung‐imaging study following CTPA is not recommended in guidelines or diagnostic algorithms, but in our institution a significant minority of physicians were employing these tests to clarify the nature of the filling defects.[20] Tapson, speaking to the treatment dilemma that small PEs present, has suggested that prospective trials on this topic employ tests that investigate risk for poor outcome if untreated including cardiopulmonary reserve, D‐dimer, and presence of lower‐limb thrombus.[21] Indeed, a study is ongoing examining the outcome at 90 days of patients with single or multiple subsegmental embolism with negative CUS.[22]

Ten of the 134 patients (7.4%) with peripheral filling defects died within 90 days. It is difficult to establish whether these deaths were PE‐specific mortalities because there was a high degree of comorbid illness in this cohort. Five of the 134 (3.7%) had recurrent VTE, which is comparable to the outcomes in other studies.[23]

There are limitations to this study. This study is the first to limit analysis of the filling defects to single defects in the segmental or subsegmental pulmonary arteries. This subset of patients includes those with the least clot burden, therefore representing the starkest decision‐making treatment dilemma, and the incidence of these clots is not insignificant. As a retrospective study, we could not fully capture all of the considerations that may have factored into the clinicians' decision‐making regarding treatment, including patient preference. Because of inadequate documentation, especially in the emergency department notes, we were unable to calculate pretest probability. Also, we cannot exclude that subclinical VTEs were occurring that would later harm the patients. We did not analyze the role of D‐dimer testing because that test is validated to guide the decision to obtain lung‐imaging studies and not to inform the treatment decision. In our cohort, 89 of 134 (66%) of our patients were already hospitalized for other diagnoses prior to PE being queried. Moreover, many of these patients had active malignancy or were being treated for pneumonia, which would decrease the positive predictive value of the D‐dimer test. D‐dimer performs poorly when used for prognosis.[24] This is a single‐center study, therefore the comparability of our findings to other centers may be an issue, although our findings generally accord with those from other single‐center studies.[7, 12, 24, 25] We determined the recurrence rate from the hospital records and could have missed cases diagnosed elsewhere. However, our hospital is the only one in the city and serves the vast majority of patients in the area, and 88% of our cohort had a repeat visit to our hospital subsequently. In addition, the radiology service is the only one in the area that provides outpatient CUS, CTPA, and ventilation‐perfusion scan studies. Our study is the largest to date on this issue. However, our sample size is somewhat modest, and consequently the factors associated with treatment have large confidence intervals. We are therefore constrained in recommending empiric application of our findings. Nonetheless, our results in terms of no difference in mortality and recurrence between treated and untreated patients are in keeping with other studies on this topic. Also, our simulation analysis did reveal factors that were highly associated with the decision to treat. These findings as a whole strongly point to the need for a larger study on this issue, because, as we and other authors have argued, the consequences of treatment are not benign.[6]

In conclusion, this study shows that SPFDs are common and that there was no difference in 90‐day mortality between treated and untreated patients, regardless of whether the defects were interpreted as PE or not. Physicians appear to rely heavily on the radiologist's interpretation for their treatment decision, but they will also treat when the interpretation is not PE and not infrequently abstain when it is. Treatment remains common despite the modest agreement among radiologists whether the peripheral filling defect even represents PE. When secondary imaging studies are obtained and negative, physicians forgo treatment. Larger studies are needed to help clarify our findings and should include decision‐making algorithms that include secondary imaging studies, because these studies may provide enough reassurance when negative to sway physicians against treatment.